dTDP-D-glucose 4,6-dehydratase (RmlB) was first identified in the L-rhamnose biosynthetic pathway, where it catalyzes the conversion of dTDP-D-glucose into dTDP-4-keto-6-deoxy-D-glucose. The ...structures of RmlB from
Salmonella enterica serovar Typhimurium in complex with substrate deoxythymidine 5′-diphospho-D-glucose (dTDP-D-glucose) and deoxythymidine 5′-diphosphate (dTDP), and RmlB from
Streptococcus suis serotype 2 in complex with dTDP-D-glucose, dTDP, and deoxythymidine 5′-diphospho-D-pyrano-xylose (dTDP-xylose) have all been solved at resolutions between 1.8 Å and 2.4 Å. The structures show that the active sites are highly conserved. Importantly, the structures show that the active site tyrosine functions directly as the active site base, and an aspartic and glutamic acid pairing accomplishes the dehydration step of the enzyme mechanism. We conclude that the substrate is required to move within the active site to complete the catalytic cycle and that this movement is driven by the elimination of water. The results provide insight into members of the SDR superfamily.
Recently a Fracture and Osteoporosis outpatient clinic (FO clinic) was set up at the University Medical Centre groningen (UMCG) with the aim to optimise case-finding of osteoporosis in older patients ...with a low-energy fracture. To provide a diagnostic setting before the start of our fo clinic, case-finding was carried out in patients who suffered an 'osteoporotic' fracture in the year prior to the foundation of the FO clinic. During a three years follow up project, osteoporotic patients who needed therapy were identified.
Patients aged 50 years or older who were seen in the UMCG for a low-energy fracture (shoulder, wrist or hip) one year before that period were asked to participate. The study was carried out in two parts - a telephone questionnaire and measurement of the bone mineral density (BMD). The data were compared with the results of the FO clinic.
Of the 191 patients, 88 could be contacted and were analysed. of these 88 patients only 12 had undergone additional investigations for the presence of osteoporosis in the year of the fracture, and only six patients were on antiosteoporosis medication; 45 patients had already suffered an earlier fracture and ten had a more recent subsequent fracture. Measurements three years after their fracture revealed that 55% of the 88 patients had osteoporosis (T-score less than -2.5 SD).
After a fracture, case-finding for osteoporosis is good clinical practice. In our study more than half of the patients were lost for follow-up after three years. But it is still worthwhile to check whether patients with fractures in the past had the necessary diagnostics and proper therapy. Comparing these results with those of the FO clinic, it is evident, however, that case-finding of osteoporosis after a fracture can be organised most effectively at the location where the patient first attends for treatment of the fracture, namely in the emergency department of the hospital.
Abstract Background Depression later in life may have a more somatic presentation compared with depression earlier in life due to chronic somatic disease and increasing age. This study examines the ...influence of the presence of chronic somatic diseases and increasing age on symptom dimensions of late-life depression. Methods Baseline data of 429 depressed and non-depressed older persons (aged 60–93 years) in the Netherlands Study of Depression in Old Age were used, including symptom dimension scores as assessed with the mood, somatic and motivation subscales of the Inventory of Depressive Symptomatology-Self Report (IDS-SR). Linear regression was performed to investigate the effect of chronic somatic diseases and age on the IDS-SR subscale scores. Results In depressed older persons a higher somatic disease burden was associated with higher scores on the mood subscale ( B =2.02, p =0.001), whereas higher age was associated with lower scores on the mood ( B =−2.30, p <0.001) and motivation ( B =−1.01, p =0.006) subscales. In depressed compared with non-depressed persons, a higher somatic disease burden showed no different association with higher scores on the somatic subscale (F(1,12)=9.2; p =0.003; partial η2 =0.022). Limitations Because the IDS-SR subscales are specific for old age, it was not feasible to include persons aged <60 years to investigate differences between earlier and later life. Conclusions It seems that neither higher somatic disease burden nor higher age contributes to more severe somatic symptoms in late-life depression. In older old persons aged ≥70 years, late-life depression may not be adequately recognized because they may show less mood and motivational symptoms compared with younger old persons.
To investigate early predictors for discharge to a geriatric rehabilitation department at a skilled nursing home in older patients after hospitalization for hip fracture surgery.
Retrospective cohort ...study.
Data from 21,176 patients with hip fracture aged ≥70 years, who were registered in the Dutch Hip Fracture Audit database between January 1, 2017, and December 31, 2019, were included.
Patients were categorized into 3 discharge groups: home (n=7326), rehabilitation (n=11,738), and nursing home (n=2112). Age, gender, Pre-Fracture Mobility Score (PFMS), premorbid Katz index of independence in Activities of Daily Living (Katz-ADL), history of dementia, American Society of Anesthesiologists physical status classification (ASA score), type of anesthesia, fracture type, surgical treatment, and cotreatment by a geriatrician were gathered. Multinomial regression analysis was used to assess for early predictors.
Higher age, poor premorbid mobility, lower premorbid Katz-ADL, no history of dementia, ASA score 3-5, general anesthesia, intramedullary implant, and cotreatment by a geriatrician were independent predictors for discharge to geriatric rehabilitation vs discharge home. Identical predictors were found for discharge to a nursing home vs discharge home. History of dementia and premorbid Katz-ADL were distinguishing factors; a higher premorbid Katz-ADL and a history of dementia were associated with a higher risk of discharge to a nursing home vs discharge home. The multinomial regression model correctly predicted 86%, 38.6%, and 2.4% of the patients in the rehabilitation group, home group, and nursing home group, respectively.
This study showed that age, PFMS, premorbid Katz-ADL, surgical treatment, ASA score, type of anesthesia, history of dementia, and cotreatment by a geriatrician were independent early predictors for discharge to geriatric rehabilitation vs discharge home in older patients after hip fracture surgery. Identical predictors were found as predictors for discharge to a nursing home vs discharge home, except for history of dementia and premorbid Katz-ADL.
Becker muscular dystrophy (BMD) is the milder allelic variant of Duchenne muscular dystrophy, with higher dystrophin levels. To anticipate on results of interventions targeting dystrophin expression ...it is important to know the natural variation of dystrophin expression between different muscles and over time. Dystrophin was quantified using capillary Western immunoassay (Wes) in the anterior tibial (TA) muscle of 37 BMD patients. Variability was studied using two samples from the same TA biopsy site in nine patients, assessing nine longitudinal TA biopsies, and eight simultaneously obtained vastus lateralis (VL) muscle biopsies. Measurements were performed in duplicate with two primary antibodies. Baseline dystrophin levels were correlated to longitudinal muscle strength and functional outcomes. Results showed low technical variability and high precision for both antibodies. Dystrophin TA levels ranged from 4.8 to 97.7%, remained stable over a 3-5 year period, and did not correlate with changes in longitudinal muscle function. Dystrophin levels were comparable between TA and VL muscles. Intra-muscle biopsy variability was low (5.2% and 11.4% of the total variability of the two antibodies). These observations are relevant for the design of clinical trials targeting dystrophin production, and may urge the need for other biomarkers or surrogate endpoints.
Background
Postsurgical thoracic aortic pseudoaneurysms (PTAPs) are a potentially lethal complication after cardiac or aortic surgery. Surgical management can pose a challenge with high in-hospital ...mortality rates. Transcatheter closure is a less-invasive alternative treatment option for selected patients, although current experience is limited.
Aims
We aimed to evaluate procedural and imaging outcomes of our first 11 cases of transcatheter PTAP closure with the use of closure devices.
Methods
Patients with a high operative risk who underwent transcatheter PTAP closure at our centre from 2019 to 2021 were retrospectively included. Suitability was evaluated on preprocedural computed tomography (CT) scans and three-dimensional (3D) reconstructions. All procedures were performed in the catheterisation laboratory. Intraprocedural aortography and postprocedural CT scans with 3D reconstructions were used to evaluate PTAP occlusion.
Results
Eleven consecutive patients with a high operative risk and a history of cardiac/aortic surgery who underwent transcatheter PTAP closure were included. PTAPs were predominantly located at the proximal or distal anastomosis of a supracoronary ascending aortic vascular graft or Bentall prosthesis (82%). Implanted closure devices included Amplatzer Valvular Plug III (82%), Amplatzer septal occluder (9%) and Occlutech atrial septal defect occluder (9%). No periprocedural complications occurred. After device deployment, residual flow was absent on aortography in 64% and minimal residual flow was present in 36% of patients. Subtotal or total occlusion of the PTAP on follow-up CT ranged between 45% and 73%.
Conclusions
Although subtotal or total occlusion of the PTAP was found at follow-up in only 45–73% of cases, transcatheter PTAP closure guided by preprocedural 3D reconstructions can offer a valuable minimally invasive primary treatment option for patients who otherwise would face a high-risk reoperation.
Introduction
Osteoporosis is a major health problem. Dual energy X-ray absorptiometry (DXA) of the hip and spine is the worldwide standard in diagnosing osteoporosis. Measurement of bone mineral ...density (BMD) with dual energy X-ray and laser absorptiometry of the calcaneus (Calscan) might be a good alternative. Advantages of the Calscan are that it is quick, widely available and manageable. In this study we compared BMD expressed in
T
-scores measured by DXA and Calscan. The aim of this study was to define threshold
T
-scores on the Calscan that could exclude or predict osteoporosis correctly in comparison with DXA.
Materials and methods
Patients ≥50 years attending our emergency department with a fracture were offered osteoporosis screening at our fracture and osteoporosis outpatient clinic (FO-Clinic) and enrolled in this study. BMD was measured at the hip and spine using DXA and at the calcaneus using Calscan. A
T
-score measured by DXA ≤−2 standard deviations (SD) below the reference population was defined as manifest osteoporosis and was the treatment threshold.
Results
During a 10-month study period, 182 patients were screened with both devices. The mean DXA-
T
-score was −1.63 SD (range −4.9 to 2.1) and Calscan
T
-score −1.91 SD (range −5.3 to 1.4). There was a significant correlation between both devices (
r
= 0.47,
P
< 0.01). Using an upper threshold for the Calscan
T
-score of −1.3 SD, 47 patients could be classified as non-osteoporotic with 89.3% sensitivity (95% CI 80.0–95.3%). Using a lower threshold for the Calscan
T
-score of −2.9 SD, 34 patients could be classified by the Calscan as osteoporotic with 90.7% specificity (95% CI 83.5–95.4). The remaining 101 patients could only be correctly classified by DXA-
T
-scores.
Conclusion
Although DXA is the established modality worldwide in measuring BMD it is restricted to specialized centres. Peripheral bone densitometers like the Calscan are widely available. When BMD measurements with DXA were compared to Calscan measurements it was possible to correctly classify 81 of 182 patients based on the Calscan
T
-score. Of these 81 patients 34 could be classified as manifest osteoporotic and 47 as non-osteoporotic. Therefore the Calscan seems to be a promising technique which might be used as a screening device at a FO-Clinic, especially when DXA is not easily available.
Scope
Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic ...health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR.
Design and methods
Nine‐week‐old male C57BL/6JRcc mice received a semi‐purified mildly obesogenic (40 en% fat) diet containing 0.14% L‐tryptophan and either 5, 15, 30, 180, or 900 mg NR per kg diet for 15 weeks. Body composition and metabolic parameters were analyzed. Metabolic flexibility was measured using indirect calorimetry. Gene expression in epididymal white adipose tissue (eWAT) was measured using qRT‐PCR .
Results
The maximum delta respiratory exchange ratio when switching from CHO to FAO (maxΔRERCHO1→FAO) and when switching from FAO to CHO (maxΔRERFAO→CHO2) were largest in 30 mg NR per kg diet (30NR). In eWAT, the gene expression of Pparγ, a master regulator of adipogenesis, and of Sod2 and Prdx3, two antioxidant genes, were significantly upregulated in 30NR compared to 5NR.
Conclusion
30NR is most beneficial for metabolic health, in terms of metabolic flexibility and eWAT gene expression, of mice on an obesogenic diet.
To determine the optimal concentration of vitamin B3 in the diet, a wide range of nicotinamide riboside (NR) was given to C57Bl/6JRcc mice. A defined human relevant diet with low tryptophan levels was used. Metabolic flexibility, serum parameters and white adipose tissue were examined. Surprisingly the effects were small. 30 mg NR/kg diet was most beneficial for metabolic health.
ObjectiveTo assess the cost effectiveness of a reduced imaging follow-up protocol of distal radius fractures compared with usual care.DesignAn economical evaluation conducted alongside a multicentre ...randomised controlled trial (RCT).SettingFour level-one trauma centres in the Netherlands.Participants341 patients participated (usual care (n=172), reduced imaging (n=169)).InterventionsPatients were randomised to usual care (routine radiography at 1, 2, 6 and 12 weeks) or a reduced imaging strategy (radiographs at 6 and 12 weeks only for a clinical indication).Outcome measuresFunctional outcome was assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and quality-adjusted life years (QALYs) using the EuroQol-5Dimensions-3 Levels (EQ-5D-3L). Costs were measured using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation, seemingly unrelated regression analysis and bootstrapping were used to analyse the data.ResultsClinical overall outcomes of both groups were comparable. The difference in DASH was −2.03 (95% CI −4.83 to 0.77) and the difference in QALYs was 0.025 (95% CI −0.01 to 0.06). Patients in the reduced imaging group received on average 3.3 radiographs (SD: 1.9) compared with 4.2 (SD: 1.9) in the usual care group. Costs for radiographic imaging were significantly lower in the reduced imaging group than in the usual care group (€−48 per patient, 95% CI −68 to −27). There was no difference in total costs between groups (€−401 per patient, 95% CI −2453 to 1251). The incremental cost-effectiveness ratio (ICER) for QALYs was −15 872; the ICER for the DASH was 198. The probability of reduced imaging being cost effective compared with usual care ranged from 0.8 to 0.9 at a willingness to pay of €20 000/QALY to €80 000/QALY.ConclusionsImplementing a reduced imaging strategy in the follow-up of distal radius fractures has a high probability of being cost effective for QALYs, without decreasing functional outcome. We, therefore, recommend imaging only when clinically indicated.Trial registration numberThe Netherlands trial register (NL4477).
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